Dental Caries Postradiotherapy in Head and Neck Cancer.

BACKGROUND: Treatment for head and neck cancer (HNC) such as radiotherapy (RT) can lead to numerous acute and chronic head and neck sequelae, including dental caries. The goal of the present study was to measure 2-y changes in dental caries after radiotherapy in patients with HNC and test risk factors for caries increment. METHODS: Cancer and dental disease characteristics, demographics, and oral health practices were documented before and 6, 12, 18, and 24 mo after the start of RT for 572 adult patients with HNC. Patients were eligible if they were age 18 y or older, diagnosed with HNC, and planned to receive RT for treatment of HNC. Caries prevalence was measured as decayed, missing, and filled surfaces (DMFS). The association between change in DMFS and risk factors was evaluated using linear mixed models. RESULTS: On average, DMFS increased from baseline to each follow-up visit: 6 mo, +1.11; 12 mo, +2.47; 18 mo, +3.43; and 24 mo, +4.29 (P < 0.0001). The increase in DMFS during follow-up was significantly smaller for the following patient characteristics: compliant with daily fluoride use (P = 0.0004) and daily oral hygiene (brushing twice daily and flossing daily; P = 0.015), dental insurance (P = 0.004), and greater than high school education (P = 0.001). DMFS change was not significantly associated with average or maximum RT dose to the parotids (P > 0.6) or salivary flow (P > 0.1). In the subset of patients who had salivary hypofunction at baseline (n = 164), lower salivary flow at follow-up visits was associated with increased DMFS. CONCLUSION: Increased caries is a complication soon after RT in HNC. Fluoride, oral hygiene, dental insurance, and education level had the strongest association with caries increment after radiotherapy to the head and neck region. Thus, intensive oral hygiene measures, including fluoride and greater accessibility of dental care, may contribute to reducing the caries burden after RT in HNC. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by clinicians when deciding how to minimize oral complications related to cancer therapy for patients with head and neck cancer. Identification of modifiable factors (e.g., oral hygiene and prescription fluoride compliance) associated with increased caries risk can minimize radiation caries burden.

Oral complications at 6 months after radiation therapy for head and neck cancer.

OBJECTIVE: To examine oral complications 6 months after modern radiation therapy (RT) for head and neck cancer (HNC). METHODS: Prospective multicenter cohort study of patients with HNC receiving intensity-modulated radiation therapy or more advanced RT. Stimulated whole salivary flow, maximal mouth opening, oral mucositis, oral pain, oral health-related quality of life (OH-QOL), and oral hygiene practices were measured in 372 subjects pre-RT and 216 subjects at 6 months from the start of RT. RESULTS: Mean stimulated whole salivary flow declined from 1.09 to 0.47 ml/min at 6 months (p < .0001). Mean maximal mouth opening reduced from 45.58 to 42.53 mm at 6 months (p < .0001). 8.1% of subjects had some oral mucositis at 6 months, including 3.8% with oral ulceration. Mean overall pain score was unchanged. OH-QOL was reduced at 6 months, with changes related to dry mouth, sticky saliva, swallowing solid foods, and sense of taste (p ≤ .0001). At 6 months, there was greater frequency of using dental floss and greater proportion using supplemental fluoride (p < .0001). CONCLUSIONS: Despite advances in RT techniques, patients with HNC experience oral complications 6 months after RT, with resulting negative impacts on oral function and quality of life.

Urban legends series: oral manifestations of HIV infection.

Human immunodeficiency virus-related oral lesions (HIV-OLs), such as oral candidiasis (OC) and oral hairy leukoplakia (OHL), have been recognized as indicators of immune suppression since the beginning of the global HIV epidemic. The diagnosis and management of HIV disease and spectrum of opportunistic infection has changed over the past 30 years as our understanding of the infection has evolved. We investigated the following controversial topics: (i) Are oral manifestations of HIV still relevant after the introduction of highly active antiretroviral therapy (HAART)? (ii) Can we nowadays still diagnose HIV infection through oral lesions? (iii) Is the actual classification of oral manifestations of HIV adequate or does it need to be reviewed and updated? (iv) Is there any novelty in the treatment of oral manifestations of HIV infection? Results from extensive literature review suggested the following: (i) While HAART has resulted in significant reductions in HIV-OLs, many are still seen in patients with HIV infection, with OC remaining the most common lesion. While the relationship between oral warts and the immune reconstitution inflammatory syndrome is less clear, the malignant potential of oral human papillomavirus infection is gaining increasing attention. (ii) Effective antiretroviral therapy has transformed HIV from a fatal illness to a chronic manageable condition and as a result expanded screening policies for HIV are being advocated both in developed and in developing countries. Affordable, reliable, and easy-to-use diagnostic techniques have been recently introduced likely restricting the importance of HIV-OLs in diagnosis. (iii) The 1993 EC-Clearinghouse classification of HIV-OLs is still globally used despite controversy on the relevance of periodontal diseases today. HIV-OL case definitions were updated in 2009 to facilitate the accuracy of HIV-OL diagnoses by non-dental healthcare workers in large-scale epidemiologic studies and clinical trials. (iv) Research over the last 6 years on novel modalities for the treatment of HIV-OLs has been reported for OC and OHL.

National prevalence of oral HPV infection and related risk factors in the U.S. adult population.

This article reviews the rapidly growing evidence that oral human papilloma viruses (HPV) infection contributes to the risk of oral squamous cell carcinoma. It also reports the first nationally representative estimates of oral HPV prevalence in the United States adult population. An estimated 7.3% (95% CI: 6.0, 8.9) of the U.S. population had one or more oral HPV types detected in oral rinse; 3.1% (95%CI: 2.4, 3.9) of the U.S. population had one or more oncogenic HPV types. A substantial excess risk of HPV infection in men is not explained by education, smoking, age of sexual debut, or number of lifetime sex partners. Based on the published finding from a case-control study, where there was an odds ratio of 2.6 (95% CI: 1.5, 4.2) for the association of head and neck cancer oncogenic oral HPV infection, the estimated population attributable risk for head and neck cancer in the U.S. population was 4.7%. In other words, there would be a 4.7% reduction in incidence rate of head and neck cancer in the United States if oncogenic HPV infection could be prevented. The results also provide population data that help evaluate the likely public health benefits of prophylactic vaccination against oral HPV acquisition.

Local drug delivery for oral mucosal diseases: challenges and opportunities.

There are few topical formulations used for oral medicine applications most of which have been developed for the management of dermatological conditions. As such, numerous obstacles are faced when utilizing these preparations in the oral cavity, namely enzymatic degradation, taste, limited surface area, poor tissue penetration and accidental swallowing. In this review, we discuss common mucosal diseases such as oral cancer, mucositis, vesiculo-erosive conditions, infections, neuropathic pain and salivary dysfunction, which could benefit from topical delivery systems designed specifically for the oral mucosa, which are capable of sustained release. Each condition requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. Local drug delivery may provide a more targeted and efficient drug-delivery option than systemic delivery for diseases of the oral mucosa. We identify those mucosal diseases currently being treated, the challenges that must be overcome and the potential of novel therapies. Novel biological therapies such as macromolecular biological drugs, peptides and gene therapy may be of value in the treatment of many chronic oral conditions and thus in oral medicine if their delivery can be optimized.

The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

(A3) HIV Phenotypes, oral lesions, and management of HIV-related disease.

Workshop participants discussed: the role of HIV subtypes in disease; the treatment of oral candidiasis; the relationship between and among viral load, CD4+ counts, oral candidiasis and oral hairy leukoplakia, pigmentation; and the development of a reliable oral index to predict disease progression. Regarding HIV, the literature revealed that Type I (HIV-I), in particular group M, is involved in the majority (90%) of documented infections, and groups N and O to a lesser extent. Viral envelope diversity led to the subclassification of the virus into nine subtypes, or clades-A-D, F-H, J, and K-each dominating in different geographical areas. HIV-2, currently occurring mostly in West Africa, appears to be less virulent. No evidence could be produced of any direct impact of type, subtype, or clade on oral lesions, and participants believed that further research is not feasible. Oral candidiasis in patients from resource-poor countries should be prevented. When the condition does occur, it should be treated until all clinical symptoms disappear. Oral rinsing with an antimicrobial agent was suggested to prevent recurrence of the condition, to reduce cost, and to prevent the development of antifungal resistance. Lawsone methyl ether, isolated from a plant (Rhinacanthus nasutus leaves) in Thailand, is a cost-effective mouthrinse with potent antifungal activity. Evidence from a carefully designed prospective longitudinal study on a Mexican cohort of HIV/AIDS patients, not receiving anti-retroviral treatment, revealed that the onset of oral candidiasis and oral hairy leukoplakia was heralded by a sustained reduction of CD4+, with an associated sharp increase in viral load. Analysis of the data obtained from a large cohort of HIV/AIDS patients in India could not establish a systemic or local cause of oral melanin pigmentation. A possible explanation was a dysfunctional immune system that increased melanin production. However, longitudinal studies may contribute to a better understanding of this phenomenon. Finally, a development plan was presented that could provide a reliable prediction of disease progression. To be useful in developing countries, the index should be independent of costly blood counts and viral load.

Extending Medicare coverage to medically necessary dental care.

BACKGROUND: Periodically, Congress considers expanding Medicare coverage to include some currently excluded health care services. In 1999 and 2000, an Institute of Medicine committee studied the issues related to coverage for certain services, including "medically necessary dental services." METHODS: The committee conducted a literature search for dental care studies in five areas: head and neck cancer, leukemia, lymphoma, organ transplantation, and heart valve repair or replacement. The committee examined evidence to support Medicare coverage for dental services related to these conditions and estimated the cost to Medicare of such coverage. RESULTS: Evidence supported Medicare coverage for preventive dental care before jaw radiation therapy for head or neck cancer and coverage for treatment to prevent or eliminate acute oral infections for patients with leukemia before chemotherapy. Insufficient evidence supported dental coverage for patients with lymphoma or organ transplants and for patients who had undergone heart valve repair or replacement. CONCLUSIONS: The committee suggested that Congress update statutory language to permit Medicare coverage of effective dental services needed in conjunction with surgery, chemotherapy, radiation therapy or pharmacological treatment for life-threatening medical conditions. PRACTICE IMPLICATIONS: Dental care is important for members of all age groups. More direct, research-based evidence on the efficacy of medically necessary dental care is needed both to guide treatment and to support Medicare payment policy.

State of the evidence base for medically necessary oral health care.

OBJECTIVE: The purpose of this article was to highlight the recent call for an evidence-based approach to public policy decision making with respect to funding dental services and the need this creates for enhanced clinical research activities. STUDY DESIGN: Systematic reviews on topics of importance to oral health care practitioners are being conducted and published by various national and international groups. Recent activities to assess evidence to support medically necessary dental services were reviewed. RESULTS: An Institute of Medicine Committee on Medicare Coverage Extensions found little published scientific evidence that directly assessed the effectiveness of dental services in preventing or managing systemic health outcomes for patients with head and neck cancer, lymphoma, leukemia, organ transplantation, and heart valve repair or replacement. CONCLUSIONS: The scientific community must strive to meet the challenge of conducting well-designed randomized, controlled trials that test the impact of dental treatment interventions on systemic health to meet the growing need for evidence to support or refute widely accepted dental treatment protocols for medically complex patients.

A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients.

OBJECTIVE: A systematic review of randomized clinical trials published between 1966 and April 2000 was undertaken to determine the strength of evidence for the effectiveness of antifungal drugs (nystatin, clotrimazole, amphotericin B, fluconazole, ketoconazole, and itraconazole) to prevent and treat oral candidiasis in human immunodeficiency virus-positive patients. STUDY DESIGN: An automated database search identified 366 articles. Six met inclusion and exclusion criteria with respect to prophylaxis; 12 met criteria for treatment of oral candidiasis. RESULTS: The evidence for the prophylactic efficacy of fluconazole is good, although insufficient to draw conclusions about the other antifungals. Evidence for treatment effectiveness is insufficient for amphotericin B but good for nystatin, clotrimazole, fluconazole, ketoconazole, and itraconazole. CONCLUSION: Suggestions for strengthening the evidence base include the following: use of larger, more well-defined groups; control for immunologic status, viral load, history of oral candidiasis, past exposure to antifungals, baseline oral Candida carriage, drug interactions, and antiretroviral therapy; and consistent use of compliance monitors, fungal speciation, and susceptibility testing.

Ability of HIV/AIDS patients to self-diagnose oral opportunistic infections.

OBJECTIVES: To assess the accuracy of HIV/AIDS patients' self-diagnosis of common HIV-related oral opportunistic infections. METHODS: 245 HIV/AIDS patients were interviewed regarding the current presence of oral candidiasis (OC), oral hairy leukoplakia (OHL), and oral ulcers prior to an oral examination by an oral medicine trained dentist examiner. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) are reported for the patient's oral lesion diagnosis compared to the dentist's diagnosis based on established presumptive clinical criteria as the gold standard. RESULTS: Self-diagnosis accuracy was greatest for pseudomembraneous OC (PPV 42.9%; NPV 93.5%), followed by oral ulcers (PPV 35.7%; NPV 98.3%) and OHL (PPV 23.5%; NPV 86.4%). Past experience with the lesion improved diagnostic accuracy, and bothersome symptoms accompanying the lesion had significant impact only for pseudomembraneous OC and oral ulcers. CONCLUSIONS: Moderate accuracy of patient self-assessment of oral lesions, with tendency to under rather than over report lesion presence, supports the use of patient self-assessment of these lesions to augment clinician diagnosis in clinical trials. Additionally, HIV/AIDS patients are unlikely to believe they have active OC that would lead to on-demand antifungal use, unless they have had prior experience with the lesion or it is at least moderately bothersome.

Sensitivity, specificity, and positive predictive value of oral opportunistic infections in adults with HIV/AIDS as markers of immune suppression and viral burden.

OBJECTIVES: The purpose of this study was to assess the use of human immunodeficiency virus (HIV)-related oral opportunistic infections as markers of immune suppression and viral burden in adults with HIV/acquired immunodeficiency syndrome (AIDS). METHODS: The population consisted of a single institution observational cohort involving 606 patients with HIV/AIDS with CD4 count data and 277 with plasma viral load measurements examined between 1995 and 1999 for the presence of oral manifestations of HIV. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value is reported for the association of specific oral lesions and lesion sets with CD4 counts <200 cells/mm(3) and with plasma HIV RNA >/=20,000 copies/mL. RESULTS: Lesions with moderate-to-high PPVs for CD4 <200 cells/mm(3) were as follows: Kaposi's sarcoma (100%; P =.035), pseudomembranous candidiasis (82. 2%; P <.001), linear gingival erythema (70.0%; P =.015), hairy leukoplakia (66.3%; P <.001), angular cheilitis (60.0%; P =.128), and erythematous candidiasis (58.3%; P =.061). Necrotizing ulcerative periodontal diseases, HIV salivary gland disease, oral ulcers, and oral warts had PPVs below 50%. Concurrent infection with candidiasis and hairy leukoplakia had the highest PPV of 89.3%; P <. 001. PPVs for HIV RNA >/=20,000 copies/mL ranged from 27.3% to 100%, with significant association only for pseudomembranous candidiasis. CONCLUSIONS: Specific common oral lesions are strongly associated with immune suppression, as measured by CD4 cell counts, and are modestly associated with high viral burden, thus serving as potential clinical markers of HIV viremia and the consequent destruction of the immune system with progressive HIV disease.

Oral and systemic factors associated with increased levels of human immunodeficiency virus type 1 RNA in saliva.

OBJECTIVE: The purpose of this investigation was to quantify human immunodeficiency virus type-1 (HIV-1) RNA in saliva and plasma and identify factors associated with increased salivary viral load. STUDY DESIGN: Forty HIV-1-seropositive adults underwent oral examinations to assess mucosal and periodontal health. Whole saliva was evaluated for HIV-1 RNA titer and occult blood. Plasma viral load, CD4 cell count, HIV-1 staging, and antiretroviral therapy data were obtained from medical records. Associations between salivary titers and oral/systemic parameters were analyzed by means of t tests, Wilcoxon signed rank tests, Pearson's correlation coefficient, and analysis of covariance. RESULTS: Forty-two percent of the subjects had detectable salivary HIV-1 RNA. Oral titers were highly correlated with plasma viral levels (r = 0.51, P <.01). HIV-associated periodontal disease (in particular, linear gingival erythema), severe gingival inflammation, and absence of antiretroviral therapy were associated with high salivary titers (P <.01). CONCLUSIONS: Substantial quantities of HIV-1 can be shed in the oral cavity, particularly when inflammatory conditions are present. Salivary titer may be a useful indicator of systemic viral burden.

Changing prevalence of oral manifestations of human immuno-deficiency virus in the era of protease inhibitor therapy.

OBJECTIVE: The purpose of this study was to determine temporal trends in the prevalence of oral manifestations of human immunodeficiency virus (HIV). STUDY DESIGN: Five hundred seventy HIV-infected adults recruited consecutively were examined by using established presumptive clinical criteria for HIV-associated oral lesions. Prevalence of oral lesions before the widespread use of HIV protease inhibitors (February 1995 through August 1996, 8% of the early sample, n = 271) was compared with lesion prevalence in a more recent period of greater protease inhibitor use (December 1996 through February 1999, 42% of the late sample, n = 299). RESULTS: Overall prevalence of oral lesions significantly decreased from early to late periods, 47.6% to 37.5%, respectively (P =.01), with some variation by lesion type. Prevalence of hairy leukoplakia (25. 8% to 11.4%; P <.01) and necrotizing periodontal diseases (4.8% to 1. 7%; P =.03) decreased, whereas HIV salivary gland disease increased (1.8% to 5.0%; P =.04). Changes in prevalence of oral candidiasis (20.3% to 16.7%), aphthous ulcers (3.7% to 3.0%), oral warts (2.2% to 4.0%), herpes simplex virus lesions (1.8% to 2.0%), and Kaposi's sarcoma (1.1% to 0.3%) were not statistically significant (P >.20 for all comparisons). CONCLUSION: The pattern of oral opportunistic infections is changing in the era of protease inhibitor use.

Oral infections and other manifestations of HIV disease.

Oral lesions are important in the clinical spectrum of HIV/AIDS, arousing suspicion of acute seroconversion illness (aphthous ulceration and candidiasis), suggesting HIV infection in the undiagnosed individual (candidiasis, hairy leukoplakia, Kaposi's sarcoma, necrotizing ulcerative gingivitis), indicating clinical disease progression and predicting development of AIDS (candidiasis, hairy leukoplakia), and marking immune suppression in HIV-infected individuals (candidiasis, hairy leukoplakia, necrotizing periodontal disease, Kaposi's sarcoma, long-standing herpes infection, major aphthous ulcers). In addition, oral lesions are included in staging systems for HIV disease progression and as entry criteria or endpoints in clinical trials of antiretroviral drugs. Recognition and management of these oral conditions is important for the health and quality of life of the individual with HIV/AIDS. In keeping with this, the U.S. Department of Health Services Clinical Practice Guideline for Evaluation and Management of Early HIV Infection includes recommendations that an oral examination, emphasizing oral mucosal surfaces, be conducted by the primary care provider at each visit, a dental examination by a dentist should be done at least two times a year, and patients should be informed of the importance of oral care and educated about common HIV-related oral lesions and associated symptoms.

Hematologic abnormalities among HIV-infected patients: associations of significance for dentistry.

OBJECTIVE: The purpose of this study was to determine the prevalence and severity of and the factors associated with peripheral blood cytopenias among HIV-infected patients. STUDY DESIGN: The investigation involved 516 HIV-infected adults in a longitudinal study of oral disease. Prevalence of hemoglobin, hematocrit, white blood cell, neutrophil, lymphocyte, and platelet values below the lower limit of normal and certain hematologic "critical values" were determined. Demographic, clinical/immunologic/viral stage, medications, and oral lesions were assessed for association with cytopenias by chi(2) and bivariate analyses. RESULTS: Findings with respect to prevalence were as follows: anemia, 51%; leukopenia, 43. 4%; neutropenia, 27.5%; lymphopenia, 20.7%; thrombocytopenia, 15.5%. Severe cytopenias were detected in fewer than 1% of the patients. Severity of HIV clinical disease and CD4 cell count depletion were significantly associated with all cytopenias. High viral load was associated only with the leukopenias. Black race, antiparasitic therapy, and some oral lesions were associated with certain cytopenias. CONCLUSIONS: In HIV-infected patients, mild cytopenias are common; however, severe anemia, neutropenia, and thrombocytopenia that may predispose to certain oral manifestations and dental surgical complications are rare.

Oral manifestations of HIV in a southeast USA population.

OBJECTIVES: Examine variations in oral manifestations of HIV by gender, race, risk behaviors, substance use and immune status in a previously unstudied population in the southeast region of the USA. DESIGN: Cross-sectional analytic study. SETTING: Academic medical center, North Carolina, USA. SUBJECTS: First 238 HIV-infected adults (76% male; 59% Black) enrolled in an ongoing longitudinal study. METHODS: Oral examination, medical chart review, sociodemographic and behavioral interview. Descriptive, bivariate, and multivariable analyses. OUTCOMES: Presence of oral manifestations of HIV. RESULTS: 50% had recent CD4 counts < 200 cells microliters-1, 48% had one or more oral lesion. Specific lesion prevalence: hairy leukoplakia (OHL) 26.5%; candidiasis (OC) 20%; HIV-associated periodontal diseases (HIV-PD) 8.8%; aphthae 4.2%; papillomas 2.5%; herpes simplex 2.1%; HIV salivary gland disease 2.1%; Kaposi's sarcoma (KS) 1.7%; other 1.3%. In bivariate analyses, OHL was associated with being male, White, having a CD4 < 200, and men who have sex with men (MSM); OC was associated with CD4 < 200 and current smoking; HIV-PD was associated with consumption of more than seven alcohol-containing drinks per week; KS was associated with being male and MSM. Significant variables in multivariable analysis for presence of any oral lesion were White, CD4 < 200, and more than seven drinks/week; for OHL were male and CD4 < 200; and for OC were White, CD4 < 200, current smoking, and not MSM. CONCLUSIONS: MSM were at increased risk for KS and OHL, not OC, while smokers were at increased risk of OC. OC, OHL, and any oral lesion were associated with immune suppression. OHL was more likely in males independent of CD4 count.